Changes of Visual Pathway and Brain Connectivity in Glaucoma: A Systematic Review

Abstract

Background: Glaucoma is a leading cause of irreversible blindness worldwide. The increasing interest in the involvement of the cortical visual pathway in glaucomatous patients is due to the implications in recent therapies, such as neuroprotection and neuroregeneration.Objective: In this review, we outline the current understanding of brain structural, functional, and metabolic changes detected with the modern techniques of neuroimaging in glaucomatous subjects.Methods: We screened MEDLINE, EMBASE, CINAHL, CENTRAL, LILACS, Trip Database, and NICE for original contributions published until 31 October 2017. Studies with at least six patients affected by any type of glaucoma were considered. We included studies using the following neuroimaging techniques: functional Magnetic Resonance Imaging (fMRI), resting-state fMRI (rs-fMRI), magnetic resonance spectroscopy (MRS), voxel- based Morphometry (VBM), surface-based Morphometry (SBM), diffusion tensor MRI (DTI).Results: Over a total of 1,901 studies, 56 case series with a total of 2,381 patients were included. Evidence of neurodegenerative process in glaucomatous patients was found both within and beyond the visual system. Structural alterations in visual cortex (mainly reduced cortex thickness and volume) have been demonstrated with SBM and VBM; these changes were not limited to primary visual cortex but also involved association visual areas. Other brain regions, associated with visual function, demonstrated a certain grade of increased or decreased gray matter volume. Functional and metabolic abnormalities resulted within primary visual cortex in all studies with fMRI and MRS. Studies with rs-fMRI found disrupted connectivity between the primary and higher visual cortex and between visual cortex and associative visual areas in the task-free state of glaucomatous patients.Conclusions: This review contributes to the better understanding of brain abnormalities in glaucoma. It may stimulate further speculation about brain plasticity at a later age and therapeutic strategies, such as the prevention of cortical degeneration in patients with glaucoma. Structural, functional, and metabolic neuroimaging methods provided evidence of changes throughout the visual pathway in glaucomatous patients. Other brain areas, not directly involved in the processing of visual information, also showed alterations.

Altered Large-Scale Brain Functional Connectivity in Ocular Hypertension

“…The traditional view of glaucoma as pure ocular condition with damage to optic nerve head and retinal ganglion cells has been recently challenged and expanded by various advanced MRI studies, which demonstrated the presence of a diffuse neurodegeneration process across the brain, also involving nonvisual system (Nuzzi et al, 2018).…”

“…Advanced magnetic resonance imaging (MRI) techniques represent a unique non-invasive approach to explore the pathogenic mechanisms of brain conditions. A number of recent studies on glaucoma have provided evidence of a neurodegenerative process across brain both within and beyond visual system (Nuzzi et al, 2018) and of various similarities with Alzheimer disease so that glaucoma may be no longer be considered a pure eye disease but rather a multifaceted and complex neurodegenerative condition.…”

The Hub-and-Spoke Management of Glaucoma

“…The essential link that unites and connects all these identities shall be the creation of a real-time computer network. clinicobiological, especially in relation to prevention and plastic condition of peripheral and central nervous system (Nuzzi and Tridico, 2017;Nuzzi et al, 2018).…”

Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte

“…Bei Störung und Zusammenbruch der Blut-Hirn-Schranke führt dies zu neuronalen Schäden, zu einer synaptischen Dysfunktion und zu einem Verlust der neuronalen Verbindungen, die zusammen in eine Neurodegeneration münden [42,43]. Diese synaptische Dysfunktion als neurodegeneratives Zeichen ist auch beim Glaukom nachgewiesen worden [9,44].…”